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Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients' survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies. [ABSTRACT FROM AUTHOR]

[Display omitted] As the fourth state of matter, plasma's unique properties and interactions with other states of matter offer many promising opportunities for investigation and discovery. In particular, cold atmospheric plasma (CAP), operating at atmospheric pressure and room temperature, has remarkable potential for biomedical applications through various delivery methods. These biomedical applications include sterilization, wound healing, blood coagulation, oral/dental diseases treatment, cancer therapy, and immunotherapy. Effective delivery of plasma constituents is critical to its efficacy for these applications. Therefore, this review presents the key research activities related to CAP delivery (including direct CAP delivery, delivery of plasma-activated media, biomedical device-assisted plasma delivery, and CAP delivery with other therapeutics) and needs for future research. This review will be of great interest for understanding the current state-of-the-art of biomedical applications of plasma medicine while also giving researchers from a broad range of communities insight into research efforts that would benefit from their contributions. Such communities include biomedicine, physics, biochemistry, material science, nanotechnology, and medical device manufacturing. [ABSTRACT FROM AUTHOR]

Seismic reflection data were used to investigate the multiple stages of headward erosion, incision, and sedimentation on the initiation and evolution of the Central Canyon, a Late Miocene-Pliocene continental slope-parallel canyon on the northwestern margin of the South China Sea. Secondary channels of the early stage generally display deep, V-shaped cross-sectional morphologies, indicating that vertical erosion was dominant in the early stage of canyon formation, while later-phase secondary channels have shallow, U-shaped cross sections, indicating that sedimentation dominated in the late stage. Influenced by gradual sea-level rise, headward erosion shifted the Central Canyon head from the Qiongdongnan Basin to the southeastern margin of the Yinggehai Basin. The length of headward erosion is up to 140 km, equivalent to one-fourth of the total length of the Central Canyon (525 km). The thalweg depth, height, and width of the Central Canyon increases down canyon from 2723 m, 164 m, and 2 km to 5318 m, 1023 m, and 16 km, respectively. This increase is gradual on gently-sloping palaeoseafloor, and more abrupt on steep-gradient palaeoseafloor. Canyon segments on gently-sloping palaeoseafloor are also characterised by a good correlation between canyon height and width. The sediments fill in the Central Canyon differ across the canyon’s segments. Turbidites and debrites infill the upstream segment of the Central Canyon. Turbidites and Mass-transport deposits are widespread in the middle reaches of the Central Canyon. The typical feature of the Central Canyon’s downstream segment is under-compensation, and canyon wall collapse are common in the upper fill of the downstream segment. We reconstruct the multistage evolution of the Central Canyon as comprising primary erosion, burial, renewed erosion, infilling, and abandonment stages. This multistage evolution was mainly controlled by relative sea-level fluctuations of the Qiongdongnan Basin. [ABSTRACT FROM AUTHOR]

Qiongdongnan Basin has a tectonic geological background of high temperature and high pressure in a deep reservoir setting, with mantle‐derived CO2. A water‐rock reaction device was used under high temperature and high pressure conditions, in conjunction with scanning electron microscope (SEM) observations, to carry out an experimental study of the diagenetic reaction between sandstone at depth and CO2‐rich fluid, which is of great significance for revealing the dissolution of deep clastic rock reservoirs and the developmental mechanism of secondary pores, promoting deep oil and gas exploration. In this study, the experimental scheme of the water‐rock reaction system was designed according to the parameters of the diagenetic background of the deep sandstone reservoir in the Qiongdongnan Basin. Three groups of single mineral samples were prepared in this experiment, including K‐feldspar samples, albite samples and calcite samples. Using CO2 as a reaction solution, a series of diagenetic reaction simulation experiments were carried out in a semi‐closed high temperature and high pressure simulation system. A field emission scanning electron microscope (SEM) was used to observe the microscopic appearance of the mineral samples after the water‐rock reaction, the characteristics of dissolution under high temperature and high pressure, as well as the development of secondary pores. The experimental results showed that the CO2‐rich fluid has an obvious dissolution effect on K‐feldspar, albite and calcite under high temperature and high pressure. For the three minerals, the main temperature and pressure window for dissolution ranged from 150°C to 300°C and 45 MPa to 60 MPa. Scanning electron microscope observations revealed that the dissolution effect of K‐feldspar is most obvious under conditions of 150°C and 45 MPa, in contrast to conditions of 200°C and 50 MPa for albite and calcite. Through the comparative analysis of experimental conditions and procedures, a coupling effect occurred between the temperature and pressure change and the dissolution strength of K‐feldspar, albite and calcite. Under high temperature and high pressure, pressure changed the solubility of CO2, furthermore, the dissolution effect and strength of the sandstone components were also affected. The experiment revealed that high temperature and high pressure conditions with CO2‐rich fluid has a significant dissolution effect on aluminosilicate minerals and is conducive to the formation of secondary pores and effective reservoirs. Going forward with the above understanding has important implications for the promotion of deep oil and gas exploration. [ABSTRACT FROM AUTHOR]

Animal parasitic diseases not only have an economic impact, but also have serious social and public health impacts. Although antiparasitic drugs can treat these diseases, it seems difficult for users to comprehensively utilize the information, due to incomplete and difficult data collection. Thus, there is an urgent need to establish a comprehensive database, that includes parasitic diseases and related drugs. In this paper, we develop a knowledge database dedicated to collecting and analyzing animal parasitic diseases and related drugs, named Animal Parasitic Diseases and Drugs Database (APDDD). The current version of APDDD includes animal parasitic disease data of 8 major parasite classifications that cause common parasitic diseases and 96 subclass samples mined from many literature and authoritative books, as well as 182 antiparasitic drugs. Furthermore, we utilized APDDD data to add a knowledge graph representing the relationships between parasitic diseases, drugs, and the targeted gene of drugs acting on parasites. We hope that APDDD will become a good database for animal parasitic diseases and antiparasitic drugs research and that users can gain a more intuitive understanding of the relationships between parasitic diseases, drugs, and targeted genes through the knowledge graph. • This is the first time that relevant data has been systematically generalized and summarized. • We employed the methodology of knowledge graph to visualize certain data in the database. • This database can become a publicly available gold standard benchmark database. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of bile duct-targeting lecithins- (PC-) coupled decorin (DCN) (PC-DCN) nanoliposomes against liver fibrosis in vitro and in vivo. We prepared PC-DCN nanoliposomes by using rat astrocytes, HSC-T6, to verify the antifibrosis effect of PC-DCN in vitro. First, we established a rat model of carbon tetrachloride-induced fibrosis. PC-DCN nanoliposomes were then injected into fibrotic rats via the portal vein or bile duct. The EdU assay was performed to analyze cell proliferation. Immunofluorescence staining was used to detect α-smooth muscle actin (α-SMA) expression. Western blot was performed to examine the expression of α-SMA, collagen type I alpha 1 (COL1A1), and transforming growth factor-β (TGF-β) protein. The levels of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TBIL) were examined by enzyme-linked immunosorbent assay (ELISA) analysis. Hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to determine liver tissue lesions and liver fibrosis. Compared with TGF-β group, PC-DCN treatment could significantly reduce cell proliferation. Western blot analysis indicated that the expression of α-SMA, COL1A1, and TGF-β was downregulated after treatment with PC-DCN in vitro and in vivo. Immunofluorescence staining confirmed that α-SMA expression was reduced by PC-DCN. Furthermore, H&E staining and Masson trichrome staining showed that the administration of PC-DCN nanoliposomes via the bile duct could reduce the extent of liver fibrosis. PCR analysis showed that PC-DCN administration could reduce proinflammatory cytokines IL-6, TNF-α, and IL-1β expression via the bile duct. The administration of PC-DCN nanoliposomes also significantly downregulated liver function indicators ALT, AST, and TBIL. The results of our study indicated that PC-DCN could effectively reduce the extent of liver fibrosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of bile duct-targeting lecithins- (PC-) coupled decorin (DCN) (PC-DCN) nanoliposomes against liver fibrosis in vitro and in vivo. We prepared PC-DCN nanoliposomes by using rat astrocytes, HSC-T6, to verify the antifibrosis effect of PC-DCN in vitro. First, we established a rat model of carbon tetrachloride-induced fibrosis. PC-DCN nanoliposomes were then injected into fibrotic rats via the portal vein or bile duct. The EdU assay was performed to analyze cell proliferation. Immunofluorescence staining was used to detect α-smooth muscle actin (α-SMA) expression. Western blot was performed to examine the expression of α-SMA, collagen type I alpha 1 (COL1A1), and transforming growth factor-β (TGF-β) protein. The levels of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TBIL) were examined by enzyme-linked immunosorbent assay (ELISA) analysis. Hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to determine liver tissue lesions and liver fibrosis. Compared with TGF-β group, PC-DCN treatment could significantly reduce cell proliferation. Western blot analysis indicated that the expression of α-SMA, COL1A1, and TGF-β was downregulated after treatment with PC-DCN in vitro and in vivo. Immunofluorescence staining confirmed that α-SMA expression was reduced by PC-DCN. Furthermore, H&E staining and Masson trichrome staining showed that the administration of PC-DCN nanoliposomes via the bile duct could reduce the extent of liver fibrosis. PCR analysis showed that PC-DCN administration could reduce proinflammatory cytokines IL-6, TNF-α, and IL-1β expression via the bile duct. The administration of PC-DCN nanoliposomes also significantly downregulated liver function indicators ALT, AST, and TBIL. The results of our study indicated that PC-DCN could effectively reduce the extent of liver fibrosis. [ABSTRACT FROM AUTHOR]

A photoredox‐catalyzed defluoroborylation of trifluoromethyl alkenes with N‐heterocyclic carbene boranes is described for the synthesis of gem‐difluoroallylboranes. This protocol exhibits a broad substrate scope and good functional group compatibility, which enables the late‐stage functionalization of structurally complex compounds. Further transformations of the defluoroborylation products to valuable CF2‐containing molecules are also demonstrated. [ABSTRACT FROM AUTHOR]

A new form of mobile payment, Quick Response (QR) code, has been a popular way of paying bus fares in China since 2017. Compared with conventional payment methods, cash or IC card, QR code shows a lot of differences in response time, recognition accuracy, and payment procedure, which significantly influences the boarding service time (BST) for passengers. However, no research has considered its efficiency. This study, therefore, tries to fill this gap and investigate its influence on BST. Sufficient ride-check data were collected, and the influence of the QR code payment method on BST was examined through a set of regression models. Passengers pay the bus fare with different payment methods as their first choice; nevertheless, when the payment fails, they may transfer among them. According to the payment choice, result, and process, we introduce the first-choice-based, the last-choice-based, and the choice-transfer-based models, respectively. The scenario with delays in calling out the QR code was considered in the choice-transfer-based model. The onboard crowdedness was regarded as a categorical variable to determine the regime of the boarding process in all models. We conduct empirical analysis in Wuhan, and this study can help to identify the influence of the QR code payment method on BST, consequently, improving bus service efficiency. [ABSTRACT FROM AUTHOR]

The paleo-Pearl River has been suggested as one of the major source terrains for the northern South China Sea, which headstreams in the hinterland of the Tibetan Plateau and flows through the South China Block, eventually discharges into the Pearl River Mouth Basin (PRMB) of the South China Sea (SCS). However, the drainage history of the paleo-Pearl River remains a matter of debate. Detrital zircon U Pb ages, trace elements, Nd and Sr isotopes and clay minerals from the Eocene to Miocene sediments in the Pearl River Mouth Basin of the South China Sea have been used to investigate the sedimentary provenance and reconstruct the drainage history of the paleo-Pearl River. The Eu/Eu*, La/Sc, La/Co, Th/Sc and Th/Co ratios, the Hf La/Th and La/Sc-Co/Th diagrams, and the chondrite normalized REE patterns of the samples suggested that the Eocene to Miocene sediments were mainly derived from felsic source rock. The Lower Eocene sediments were mainly provided by the intrabasinal uplift regions. The Dong River and Bei River initiated since Upper Eocene supplied large amounts of felsic detritus from the Southern China Coast to Zhu Ⅰ Depression, and then transported sediments into the Zhu Ⅱ depression during the upper Early Oligocene. The Nd and Sr isotopes of the sediments suggested that the Liu River may not provide sediments for the PRMB, however, the Gui River may have made a very small contribution. The Nd and Sr isotopes of the sediments also suggested that the paleo-Pearl River began to extend westward to form Xi River and eventually the Hongshui River in the Late Oligocene. The trace element ratios of the samples also suggested that the Miocene sediments may have received more input from an intermediate rock area, indicating the main provenance switch from the coast of South China to a northern source during this time. This conclusion has been supported by the detrital zircon U Pb ages, Nd and Sr isotopes and clay minerals data of the samples, which show that the provenance of the sediments supplied by the paleo-Pearl River had an abrupt shift in the Middle Miocene. The southeastern Tibetan Plateau rapid uplifted and experienced erosion in the Middle Miocene, leading to the progressive headward erosion of the Pearl River system into the continental interior. Detrital zircon U Pb ages, trace elements, Nd and Sr isotopes and clay minerals of Eocene to Miocene samples for the PRMB have been used to determine the provenance of the PRMB and reconstruct the evolutionary history of the paleo-Pearl River. The following conclusions can be made: (1) The Oligocene to Miocene sediments transported by the paleo-Pearl River were derived from felsic source rock and the Miocene sediments may have received more input from intermediate rock area. (2) The Liu River might not provide sediments for the PRMB and the Gui River might have made a very small contribution. The paleo-Pearl River began to extend westward to form the Xi River and eventually the Hongshui River was formed during the Late Oligocene. (3) Trace elements and Nd and Sr isotopes of the samples indicated that the western tributaries of the Pearl River did act as important sediment supplier since Early Miocene and lasted to Middle Miocene. (4) The provenance abrupt change in the Middle Miocene probably resulted from the rapid uplift of the southeastern Tibetan Plateau, leading to the progressive headward erosion of the Pearl River system into the continental interior on the basis of the Early Miocene. [ABSTRACT FROM AUTHOR]

Paddy fields located around estuaries suffer from seawater intrusion, and how and to what extent salinity levels influence Cd accumulation in rice grains is still unclear. Pot experiments were carried out by cultivating rice under alternating flooding and drainage conditions with different salinity levels (0.2‰, 0.6‰ and 1.8‰). The Cd availability was greatly enhanced at 1.8‰ salinity due to the competition for binding sites by cations and the formation of Cd complexation with anions, which also contributed to Cd uptake by rice roots. The soil Cd fractions were investigated and found that the Cd availability significantly decreased during flooding stage, while it rapidly increased after soil drainage. During drainage stage, Cd availability was greatly enhanced at 1.8‰ salinity mainly attributed to the formation of CdCl n 2−n. The kinetic model was established to quantitatively evaluate Cd transformation, and it found that the release of Cd from organic matter and Fe-Mn oxides was greatly enhanced at 1.8‰ salinity. The results of pot experiments showed that there was a significant increase in Cd content in rice roots and grains in the treatment of 1.8‰ salinity, because the increasing salinity induced an increase in Cd availability and upregulation of key genes regulating Cd uptake in rice roots. Our findings elucidated the key mechanisms by which high salinity enhanced Cd accumulation in rice grains, and more attention should be given to the food safety of rice cultivated around estuaries. [Display omitted] • Cd accumulation in rice was significantly increased at 1.8‰ salinity. • Cations and anions promoted Cd release from solid phases during drainage stage. • High salinity increased expression levels of Cd uptake genes in rice roots. • Kinetic models were used to quantitatively evaluate the Cd transformation. [ABSTRACT FROM AUTHOR]

Chromium isotopes are promising for monitoring and quantifying the extent of microbial Cr(VI) reduction. However, the mechanisms and factors that influence Cr isotope fractionation are not well understood. In the present study, we investigated the effects of different metabolic pathways and various environmental parameters on Cr isotope fractionation during Cr(VI) reduction by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus. The Cr isotopic compositions were measured on unreacted Cr(VI) in the remaining solution. The reaction product is isotopically lighter than the reactant. The Cr isotope composition for remaining Cr(VI) in the solution followed a Rayleigh fractionation trend and thus became increasingly isotopically heavier as the reduction of Cr(VI) proceeded. Cr(VI) reduction mainly occurs on the cell surface by Ni–Fe hydrogenase; however, in the presence of CuCl 2 , the activity of Ni–Fe hydrogenase was inhibited, and Cr(VI) was reduced inside the cells. We found that despite different Cr(VI) reduction locations, Cr isotope enrichment factors (ε = (α − 1) × 1000, where α is the fractionation factor) were identical within uncertainty for experiments with and without CuCl 2 (−2.72 ± 0.67‰ and −2.92 ± 0.14‰, respectively). When added to the cell cultures, neutral red (NR) functioned as an electron carrier that enabled bacteria to drive the electron transfer processes. The ε values were also similar for experiments with and without NR (−2.53 ± 0.40‰ and −2.92 ± 0.14‰, respectively). We compared these ε values to investigate the effects of different electron transport pathways and cellular Cr(VI) transfer processes, including Cr(VI) transport across the cell envelope and binding to reacting enzymes, on Cr isotope fractionation. Furthermore, the effects of various environmental parameters on Cr isotope fractionation were tested, including temperature (50 °C and 70 °C), hydrogen concentration, and different electron donors (glucose and hydrogen). The ε values were similar at both tested temperatures and stayed within the previously observed range for mesophiles; changes in hydrogen concentration also did not affect the ε values. However, the ε values were slightly higher with hydrogen as the electron donor (−3.64 ± 0.24‰) than those with glucose as the electron donor (−2.92 ± 0.14‰). In short, the Cr enrichment factors remained unchanged despite of changing microbial Cr (VI) reduction pathways and changing temperature conditions, but may be sensitive to the electron donor type. [ABSTRACT FROM AUTHOR]

Abstract Chromium isotope fractionation analysis is a promising approach for the assessment of microbial Cr(VI) reduction in groundwater. Understanding the mechanisms and other parameters that control Cr isotope fractionation factors (between the product Cr(III) and reactant Cr (VI)) in microbial Cr(VI) reduction is critical to this application. To date, such studies are very limited. Here, the influence of critical factors on observed Cr isotope fractionation during Cr(VI) reduction by Shewanella oneidensis MR-1 under various conditions was investigated. The Cr(VI) concentration and Cr isotope ratio measurements were conducted on unreacted Cr(VI) remaining in solution to determine Cr isotope fractionation factors. The changes in ambient environmental conditions (e.g., pH, temperature) have limited influence on Cr isotope fractionation factors. However, as a result of Cr(VI) consumption as the experiments proceed, the change in bioavailability of Cr(VI) has a significant impact on Cr isotope fractionation factors. For example, in temperature-controlled experiments, Cr isotope fractionation showed two-stage behavior: during Stage I, the values of ε were −2.81 ± 0.19‰ and −2.60 ± 0.14‰ at 18 °C and 34 °C, respectively; during Stage II, as Cr(VI) reduction progressed, Cr isotope fractionation was significantly masked, and the ε values decreased to −0.98 ± 0.49‰ and −1.01 ± 0.11‰ at 18 °C and 34 °C, respectively. Similar two-stage isotope fractionation behaviors were observed in pH-controlled experiments (pH = 6.0 and 7.2) and in experiments with and without the addition of a competing electron acceptor (nitrate). Masking of isotope fractionation in Stage II indicated restrictions on the bioavailability of Cr(VI) and mass-transfer limitations. This study provides an explanation for the variation in Cr isotope fractionation factors during microbial Cr(VI) reduction in the environment, furthering the viability of Cr isotope ratio analysis as an approach in understanding Cr biogeochemical cycling. Graphical abstract Image 1 Highlights • Two-stage process of microbially induced Cr isotope fractionation was revealed. • The suppression of fractionation was attributed to mass-transfer limitations. • Temperature and pH have limited influence on microbially induced fractionation. • The values of ε were similar in the presence or in the absence of nitrate. [ABSTRACT FROM AUTHOR]

There is a controversy regarding the source area and weathering intensity of Oligocene to Lower Miocene sediments in the Baiyun Sag of the Pearl River Mouth Basin. Detrital modes, geochemistry, heavy mineral data, and detrital zircon U–Pb ages were analysed to understand the provenance, source area weathering, and tectonic setting of Oligocene to Lower Miocene sandstones in the Baiyun Sag. Petrographic data reveal that the sandstones were derived from a recycled orogen. With increasing transport distance, sediment maturity increased correspondingly. The Oligocene to Lower Miocene sandstones in the Baiyun Sag have low compositional maturity and have experienced low to moderate weathering. The sediments of the Zhuhai Formation have experienced relatively strong weathering intensity compared with those of the Enping and lower Zhujiang formations. Due to low degree of illitization and differences in the geochemical compositions of the sediments, the continental island arc data from different boreholes in the Baiyun Sag are more irregularly distributed in the A‐CN‐K plot. The modal composition (e.g., quartz, feldspar, and lithic fragments) and geochemical indices (Al2O3/TiO2 ratio; Al2O3‐TiO2 diagram; discriminant F1‐F2 diagram; Eu/Eu*, La/Sc, La/Co, Th/Sc, and Th/Co ratios; Hf‐La/Th and La/Sc‐Co/Th diagrams; and rare earth element patterns) indicate that the sediments in the Baiyun Sag are mainly derived from felsic source rocks. Although the uplift around the Baiyun Sag includes multistage magmatism and basic rocks, it has little influence on the sediment in the depression, and no sediments were transported by the Han River to the Baiyun Sag. Geochemical data and detrital zircon U–Pb ages suggest that the Pearl River was formed in the Early Oligocene and became the main source for the sediments in this area. The river carried felsic material from the South China Coast forming a large delta on the northern slope of the Baiyun Sag. The ratios of Eu/Eu*, La/Sc, La/Co, Th/Sc and Th/Co, and heavy mineral data indicate that the sediments transported by the Pearl River to the Baiyun Sag were changed from the arc‐dominated coastal zone to the interior of the South China Block during the Late Oligocene to Early Miocene and even reached the south‐eastern margin of the Tibetan Plateau (West Yunnan Plateau). The La‐Th‐Sc and Th‐Sc‐Zr/10 diagrams suggest that the provenance of these sandstones is evolved continental island arc or an active continental margin setting. [ABSTRACT FROM AUTHOR]

A Co(II)-catalyzed direct C3-selective C-H acyloxylation of indoles has been realized with tert-butyl peresters serving as both an acyloxy source and an oxidant. This reaction features highly C3 regioselectivity and good functional group tolerance, which provides a convenient and versatile approach to the construction of valuable 3-acyloxyindoles in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti -restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti -restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications. [ABSTRACT FROM AUTHOR]

An efficient palladium/copper-catalyzed tandem Sonogashira reaction/lactonization of methyl 2-(2′,2′-dibromovinyl)benzoate with terminal alkynes has been developed. This facile and direct approach furnishes a variety of 3-alkynyl isocoumarins in moderate to good yields under mild reaction conditions. Furthermore, this method enables concise total synthesis of natural products 3′-hydroxycorfin and gymnopalynes A. [ABSTRACT FROM AUTHOR]

Spatiotemporal control over the release or activation of biomacromolecules such as siRNA remains a significant challenge. Light-controlled release has gained popularity in recent years; however, a major limitation is that most photoactivable compounds/systems respond only to UV irradiation, but not near-infrared (NIR) light that offers a deeper tissue penetration depth and better biocompatibility. This paper reports a simple NIR-to-UV upconversion nanoparticle (UCNP)-based siRNA nanocarrier for NIR-controlled gene silencing. siRNA is complexed onto a NaYF 4 :Yb/Tm/Er UCNP through an azobenzene (Azo)–cyclodextrin (CD) host–guest interaction. The UV emission generated by the NIR-activated UCNP effectively triggers the trans -to- cis photoisomerization of azobenzene, thus leading to the release of siRNA due to unmatched host − guest pairs. The UCNP-siRNA complexes are also functionalized with PEG (i.e., UCNP-(CD/Azo)-siRNA/PEG NPs), targeting ligands (i.e., EGFR-specific GE11 peptide), acid-activatable cell-penetrating peptides (i.e., TH peptide), and imaging probes (i.e., Cy5 fluorophore). The UCNP-(CD/Azo)-siRNA/PEG NPs with both GE11 and TH peptides display a high level of cellular uptake and an excellent endosomal/lysosomal escape capability. More importantly, NIR-controlled spatiotemporal knockdown of GFP expression is successfully achieved in both a 2D monolayer cell model and a 3D multicellular tumor spheroid model. Thus, this simple and versatile nanoplatform has great potential for the selective activation or release of various biomacromolecules. [ABSTRACT FROM AUTHOR]

Polymeric unimolecular nanoparticles (NPs) exhibiting a core-shell structure and formed by a single multi-arm molecule containing only covalent bonds have attracted increasing attention for numerous biomedical applications. This unique single-molecular architecture provides the unimolecular NP with superior stability both in vitro and in vivo, a high drug loading capacity, as well as versatile surface chemistry, thereby making it a desirable nanoplatform for therapeutic and diagnostic applications. In this review, we surveyed the architecture of various types of polymeric unimolecular NPs, including water-dispersible unimolecular micelles and water-soluble unimolecular NPs used for the delivery of hydrophobic and hydrophilic agents, respectively, as well as their diverse biomedical applications. Future opportunities and challenges of unimolecular NPs were also briefly discussed. [ABSTRACT FROM AUTHOR]

Background/Aims: In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. Methods: Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. Results: A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, P< 0.05). QRT-PCR results of five dysregulated genes were consistent with HTS data. A lncRNA-mRNA coexpression analysis showed positive correlations between the up-regulated lncRNA (ENSG00000269936) and its adjacent up-regulated mRNA (MAP2K6, R=0.940, P< 0.01), and between the down-regulated lncRNA_1421 and its down-regulated mRNAs (FBLN5, R=0.950, P< 0.01; ACTA2, R=0.96, P< 0.01; TIMP3, R=0.96, P< 0.05). The lncRNA-miRNA-mRNA network indicated that the up-regulated lncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p. The results of luciferase assay and fluorescence immuno-cytochemistry were consistent with that. And qRT-PCR results showed that lncRNA XIST and p21 were expressed at a higher level and has-miR-17-5p was expressed at a lower level in TAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, P< 0.001; R=0.967, P< 0.01; R=0.960, P< 0.01, respectively). Conclusions: Our study revealed a set of dysregulated lncRNAs and predicted their multiple potential functions in human TAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD. [ABSTRACT FROM AUTHOR]

A unique pH/redox dual-sensitive cationic unimolecular nanoparticle (NP) enabling excellent endosomal/lysosomal escape and efficient siRNA decomplexation inside the target cells was developed for tumor-targeted delivery of siRNA. siRNA was complexed into the cationic core of the unimolecular NP through electrostatic interactions. The cationic core used for complexing siRNA contained reducible disulfide bonds that underwent intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH) inside the cells, thereby facilitating the decomplexation of siRNA from the unimolecular NPs. The cationic polymers were conjugated onto the hyperbranched core (H40) via a pH-sensitive bond, which further facilitated the decomplexation of siRNA from the NPs. In vitro studies on the siRNA release behaviors showed that dual stimuli (pH = 5.3, 10 mM GSH) induced the quickest release of siRNA from the NPs. In addition, the imidazole groups attached to the cationic polymer segments enhanced the endosomal/lysosomal escape of NPs via the proton sponge effect. Intracellular tracking studies revealed that siRNA delivered by unimolecular NPs was efficiently released to the cytosol. Moreover, the GE11 peptide, an anti-EGFR peptide, enhanced the cellular uptake of NPs in MDA-MB-468, an EFGR-overexpressing triple negative breast cancer (TNBC) cell line. The GE11-conjugated, GFP-siRNA-complexed NPs exhibited excellent GFP gene silencing efficiency in GFP-MDA-MB-468 TNBC cells without any significant cytotoxicity. Therefore, these studies suggest that this smart unimolecular NP could be a promising nanoplatform for targeted siRNA delivery to EFGR-overexpressing cancer cells. [ABSTRACT FROM AUTHOR]

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)-based theranostic micelles are developed for NET-targeted and near-infrared (NIR)-controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light-sensitive amphiphilic block copolymers poly(4,5-dimethoxy-2-nitrobenzyl methacrylate)-polyethylene glycol (PNBMA-PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR-activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR-induced hydrophobic-to-hydrophilic transition of the micelle core and thus enabling NIR-controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate 1O2 for NIR-induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET-targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3-loaded UCNP-based micelles conjugated with RB and KE108-enabling NET-targeted combination chemotherapy and PDT-induce the best antitumor efficacy. [ABSTRACT FROM AUTHOR]

Glaucoma is a common blinding disease characterized by loss of retinal ganglion cells (RGCs). To date, there is no clinically available treatment directly targeting RGCs. We aim to develop an RGC-targeted intraocular drug delivery system using unimolecular micelle nanoparticles (unimNPs) to prevent RGC loss. The unimNPs were formed by single/individual multi-arm star amphiphilic block copolymer poly(amidoamine)–polyvalerolactone–poly(ethylene glycol) (PAMAM–PVL–PEG). While the hydrophobic PAMAM–PVL core can encapsulate hydrophobic drugs, the hydrophilic PEG shell provides excellent water dispersity. We conjugated unimNPs with the cholera toxin B domain (CTB) for RGC-targeting and with Cy5.5 for unimNP-tracing. To exploit RGC-protective sigma-1 receptor (S1R), we loaded unimNPs with an endogenous S1R agonist dehydroepiandrosterone (DHEA) as an FDA-approved model drug. These unimNPs produced a steady DHEA release in vitro for over two months at pH 7.4. We then co-injected (mice, intraocular) unimNPs with the glutamate analog N -methyl- d -aspartate (NMDA), which is excito-toxic and induces RGC death. The CTB-conjugated unimNPs (i.e., targeted NPs) accumulated at the RGC layer and effectively preserved RGCs at least for 14 days, whereas the unimNPs without CTB (i.e., non-targeted NPs) showed neither accumulation at nor protection of NMDA-treated RGCs. Consistent with S1R functions, targeted NPs relative to non-targeted NPs showed markedly better inhibitory effects on apoptosis and oxidative/inflammatory stresses in the RGC layer. Hence, the DHEA-loaded, CTB-conjugated unimNPs represent an RGC/S1R dual-targeted nanoplatform that generates an efficacious template for further development of a sustainable intraocular drug delivery system to protect RGCs, which may be applicable to treatments directed at glaucomatous pathology. [ABSTRACT FROM AUTHOR]

Greenhouse gas (GHG) emissions from oil and gas exploration and development are major contributors to emission inventories in oil and natural gas (ONG) systems. For the developing countries, including China, studies of this aspect of the industry, being at an early stage, lack a unified method of calculation, and this leads to varied projections of national emissions. In this paper, progress is reported on direct measurement of CH 4 and CO 2 emissions along the oil and gas value chain, for four oil and gas fields. An improved calculation method (classification calculation method), which considers the production status of each type of oil and gas field in China, is proposed for the first time in this study. Based on in situ measurement, it is used to estimate the national CH 4 and CO 2 emissions from the process of petroleum exploration and development. The results showed that CH 4 and CO 2 emissions in 2013 were 73.29 × 10 4 and 20.32 × 10 4 tonnes, respectively (in CO 2 equivalent: 1559.36 × 10 4 tonnes). Compared with the results (731.52 × 10 4 tonnes of CH 4 , 1031.55 × 10 4 tonnes of CO 2 , 16,393.48 × 10 4 tonnes of CO 2 equivalent) in 2013 determined by the Tier 1 method of the Intergovernmental Panel on Climate Change (IPCC), the carbon emissions from field measurement method were much lower than that of IPCC method, which indicated that carbon emissions of ONG systems in China were severely overrated by IPCC. Hence, the GHG emission results reported herein could fundamentally improve the knowledge and understanding of GHG emissions from ONG exploration and development in China. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loaded, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF-loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) cancers can cause significant patient morbidity. Besides surgery, there are no curative treatments for NE cancers and their metastases, emphasizing the need for the development of other forms of therapy. In this study, multifunctional unimolecular micelles were developed for targeted NE cancer therapy. The unimolecular micelles were formed by multi-arm star amphiphilic block copolymer poly(amidoamine)–poly(valerolactone)–poly(ethylene glycol) conjugated with KE108 peptide and Cy5 dye (abbreviated as PAMAM–PVL–PEG–KE108/Cy5). The unimolecular micelles with a spherical core–shell structure exhibited a uniform size distribution and excellent stability. The hydrophobic drug thailandepsin-A (TDP-A), a recently discovered HDAC inhibitor, was physically encapsulated into the hydrophobic core of the micelles. KE108 peptide, a somatostatin analog possessing high affinity for all five subtypes of somatostatin receptors (SSTR 1–5), commonly overexpressed in NE cancer cells, was used for the first time as an NE cancer targeting ligand. KE108 exhibited superior targeting abilities compared to other common somatostatin analogs, such as octreotide, in NE cancer cell lines. The in vitro assays demonstrated that the TDP-A-loaded, KE108-targeted micelles exhibited the best capabilities in suppressing NE cancer cell growth. Moreover, the in vivo near-infrared fluorescence imaging on NE-tumor-bearing nude mice showed that KE108-conjugated micelles exhibited the greatest tumor accumulation due to their passive targeting and active targeting capabilities. Finally, TDP-A-loaded and KE108-conjugated micelles possessed the best anticancer efficacy without detectable systemic toxicity. Thus, these novel TDP-A-loaded and KE108-conjugated unimolecular micelles offer a promising approach for targeted NE cancer therapy. [ABSTRACT FROM AUTHOR]

• Bus bunching occurs much fewer in observations than in conventional models. • Counteraction between link and stop headway deviations can resist bus bunching. • Superposition between link and stop headway deviations destroys headway regularity. • Counteraction is more prominent than superposition with buses moving forward. • The counteraction effect owes to drivers' reactions to bus travel time deviations. Bus headway deviations are the major causes of bus bunching, which is detrimental to bus service reliability and leads to excessive waiting time for passengers. Generally, it is believed that bus bunching is an inevitable result once a service disturbance occurs, as long as the route is long enough. However, in this study, it goes as low as 5% of all trips from the empirical data, contradicting the expectation in theory. This study explores the underlying reasons for this contradiction based on empirical data from two representative bus routes in China. The results show that headway deviations on links and at stops mostly counteract with each other, constraining the occurrence of bus bunching. Under this counteraction effect, the path headway deviations remain within a stable range, normally bounded by the planned headway. It indicates that the bus system has a self-repair ability to resist headway disruptions, which explains why bus bunching happens at a considerably lower frequency in practice than in theory. We further discuss how the counteraction effect works. The insights gained from this study can shed light on preventing bus bunching and generating new ways to recover bus service regularity after a headway disruption. If we can adequately adjust the control methods to make the link and stop headway deviations counteract with each other, the bus system can automatically mitigate the headway deviations. [ABSTRACT FROM AUTHOR]

Biocompatible nanoparticles of gadolinium-incorporated Prussian blue with the empirical formula K0.94Gd0.02Fe[Fe(CN)6] exhibit extremely high stability against the release of Gd3+ and CN− ions under the acidic conditions similar to stomach juice. The high r1 relaxivity, low cytotoxicity and the ability of such nanoparticles to penetrate the cell membrane suggest that this coordination-polymer structural platform offers a unique opportunity for developing the next generation of T1-weighted oral cellular MRI probes for the early detection of tumors in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods: 25-hydroxyvitamin D loaded poly(-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. Results: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D. The duration of 25-hydroxyvitamin D release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions: Plasma treated and 25-hydroxyvitamin D loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity. [ABSTRACT FROM AUTHOR]

The Qiongdongnan Basin (QDNB) is a petroleum-bearing basin in the northern margin of the South China Sea (SCS). Provenance analysis is an important tool in petroleum exploration and is helpful in predicting the distribution of good reservoirs in areas with less drilling. However, the provenance of the QDNB remains controversial, and further research is needed. Here, we apply whole-rock geochemistry, petrography, and heavy minerals combined with published detrital zircon U-Pb ages to constrain the provenance of Oligocene to middle Miocene sandstones in the QDNB and the tectonic environment of their deposition. The Oligocene to middle Miocene sandstones from the QDNB are geochemically immature. These sandstones were derived from a weakly weathered source area characterized by dominantly felsic igneous rocks, with a particular slight addition from recycled sedimentary sources. And the Lingshui Formation underwent less weathering than the upper and lower strata. The tectonic setting of the sandstones in the basin belongs to a continental island arc (CIA) or an active continental margin (ACM). Heavy mineral assemblages and detrital zircon U-Pb ages reveal sediment input from multiple sources. Hainan Island was a major and continuous source area contributing to the basin from the early Oligocene to the middle Miocene. In addition, intrabasinal uplift regions could have supplied material to local areas. While these sedimentary source patterns appear to have changed very little in the late Oligocene, a provenance from central Vietnam was explicitly discerned in the western QDNB in the late Oligocene. It is possible that the paleo-Pearl River supplied large volumes of sediment to the eastern QDNB from the late Oligocene to the early Miocene. • The sandstones from the QDNB are generally considered chemically and texturally immature to submature and they experienced a low degree of weathering in their source areas. The Lingshui Formation also underwent less weathering than the upper and lower strata. • These sediments were largely from felsic igneous source rocks, with a particular slight addition from recycled sedimentary sources, which originated in a continental island arc (CIA) and active continental margin (ACM) setting. • Hainan Island is likely to have been the dominant and stable source of the detritus from the early Oligocene to the middle Miocene, a provenance from central Vietnam is explicitly discerned in the western QDNB in the late Oligocene. It is possible that a dominant sedimentary contribution from the paleo-Pearl River to the eastern QDNB occurred during the late Oligocene–early Miocene. [ABSTRACT FROM AUTHOR]

A novel type of self-fluorescent unimolecular micelle nanoparticle (NP) formed by multi-arm star amphiphilic block copolymer, Boltron ® H40 (H40, a 4th generation hyperbranched polymer)- b iodegradable p hoto- l uminescent p olymer (BPLP)-poly(ethylene glycol) (PEG) conjugated with cRGD peptide (i.e., H40-BPLP-PEG-cRGD) was designed, synthesized, and characterized. The hydrophobic BPLP segment was self-fluorescent, thereby making the unimolecular micelle NP self-fluorescent. cRGD peptides, which can effectively target α v β 3 integrin-expressing tumor neovasculature and tumor cells, were selectively conjugated onto the surface of the micelles to offer active tumor-targeting ability. This unique self-fluorescent unimolecular micelle exhibited excellent photostability and low cytotoxicity, making it an attractive bioimaging probe for NP tracking for a variety of microscopy techniques including fluorescent microscopy, confocal laser scanning microscopy (CLSM), and two-photon microscopy. Moreover, this self-fluorescent unimolecular micelle NP also demonstrated excellent stability in aqueous solutions due to its covalent nature, high drug loading level, pH-controlled drug release, and passive and active tumor-targeting abilities, thereby making it a promising nanoplatform for targeted cancer theranostics. [ABSTRACT FROM AUTHOR]

Tumor‐associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor‐associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll‐like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell‐triggered lipolysis. Locally administered drug‐loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug‐loaded adipocytes improved CD8+ T cell‐mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes. [ABSTRACT FROM AUTHOR]

In the transition metal-catalyzed cross-coupling reactions, phenol and enol derivatives activated by phosphorus groups are very important electrophiles. This kind of compounds has the advantages of easy preparation, great stability, and producing more benign phosphorus by-products. The present work provides a comprehensive review of the advances made over the past several decades in this area. Cross-coupling reactions mediated by PyBroP are first surveyed, then two types of recently developed transition metal-catalyzed reactions, i.e., Pd-catalyzed and Ni-catalyzed reactions, and the corresponding mechanisms are discussed. Finally, future directions are analyzed. [ABSTRACT FROM AUTHOR]

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. [ABSTRACT FROM AUTHOR]

At the terminal station, the path headway bias of a trip is linearly correlated to the travel time of the path when it is beyond a critical range, which marks the tendency between successive trips. A tendency-based model for trajectory prediction was proposed in which the path headway bias was assumed to be proportionally amplified at downstream stops with an increase in path travel time, when buses fall into the amplifying tendency, or remain the same, when buses fall into the maintaining tendency. The boundary of the tendency was calibrated by the relative performance between the proportion-based model and the history-based model. The calibrated tendency-based model succeeds in avoiding the amplification of nondirectional path headway bias in the proportion-based model by keeping buses in the maintaining tendency and promoting the amplification of directional path headway bias by allowing buses to fall into the amplifying tendency. [ABSTRACT FROM AUTHOR]

From the historical bus trajectories, it was found that the headway bias amplified as buses travel on the route. When controls on buses are unavailable, the following buses will maintain the movement tendency toward their previous one, whether being closer to, farther away, or stable, judged by the running state in which buses fall. A tendency-based model for link travel time estimation was proposed, and three tendency-based corrections were introduced in the model, which are the long-term tendency, the short-term tendency, and the combined-term tendency. Then, contrast experiments were conducted in which the boundary of the running state is a control variable to show the performance of the tendency-based model under different boundary values. The experiment results show that, with the increase of the boundary value, the degree of improvement of the tendency-based mode to the historical data-based model first increases, then decreases, and converges to zero finally. The optimal boundary value for the tendency-based model was calibrated, judged by the net number of trips improved and net mean absolute error reduced, and the results show that the long-term and the combined-term tendency-based models have a lower optimal boundary and higher optimization potential, and are faster to be steady enough, which made the short-term tendency-based model less competitive. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel real-time rendering algorithm for heterogenous translucent objects with deformable geometry. The proposed method starts by rendering the surface geometry in two separate geometry buffers-the irradiance buffer and the splatting buffer-with corresponding mipmaps from the lighting and viewing directions, respectively. Irradiance samples are selected from the irradiance buffer according to geometric and material properties using a novel and fast selection algorithm. Next, we gather the irradiance per visible surface point by splatting the irradiance samples to the splatting buffer. To compute the appearance of long-distance low-frequency subsurface scattering, as well as short-range detailed scattering, a fast novel multiresolution GPU algorithm is developed that computes everything on the fly and which does not require any precomputations. We illustrate the effectiveness of our method on several deformable geometries with measured heterogeneous translucent materials. [ABSTRACT FROM AUTHOR]

Non-technical summary Women during their child-bearing years have longer QT intervals in their electrocardiograms than men and are more susceptible to lethal arrhythmias elicited by drugs that delay repolarization. Current theories posit that women have a reduced 'repolarization reserve' due to reduced potassium currents resulting in longer QT and greater repolarization delays. We proposed an alternative mechanism of higher calcium currents in women which would likewise prolong QT intervals, delay repolarization while increasing the force of contractions and intracellular calcium load. Here, we show that physiological concentrations of oestrogen increase the calcium current only in cells from the base of the heart, by increasing messenger RNA and proteins levels that encode for the calcium current. Moreover, oestrogen acts by interacting with oestrogen receptors (ER)α but not ERβ which may explain why hormone replacement therapy increases the risk of arrhythmia and offers a possible protective solution of using an oestrogen mimetic that selectively binds to ERβ. [ABSTRACT FROM AUTHOR]

Bus-arrival-time information service is a key component of an advanced transit information system. Instantaneous and accurate prediction of bus arrival time can help improve the quality of service, and attracts additional ridership. On the bases of analyses of bus running processes, bus arrival time was divided into interzone link travel time and section travel time. A self-adaptive exponential smoothing-based algorithm was proposed for interzone link travel time prediction, whereas link-based and section-based algorithms were proposed for section travel time prediction. With the automatic vehicle location data collected from an actual bus route, an experiment was conducted to measure the performance (accuracy and precision in prediction) of link-based and section-based models with respect to three dominant factors: day of week, time of day, and length of segment. The research results show that: (1) the overall performance of section-based models is superior to that of link-based models on all weekdays but Monday, and few differences exist on weekends between link-based and section-based models; (2) section-based models perform significantly better than link-based models during periods when traffic conditions are relatively better; (3) as the vehicle approaches the target stop, the accuracy of prediction decreases and the precision of prediction increases for both link-based and section-based models. In addition, the performance of section-based models is superior to that of link-based models, but the gap narrows gradually with decreases length of segment. [ABSTRACT FROM AUTHOR]

Women of child bearing age are known to have longer QT intervals on their electrocardiogram recordings due to sex-differences in the heart that are mediated by the sex hormone oestrogen. This results in a higher risk of lethal arrhythmias in women when their QT interval is prolonged further through drugs or inherited congenital diseases (i.e. long QT syndrome). Using rabbit hearts, which exhibit the same sex-differences as in humans, it is here shown for the first time that oestrogen up-regulates the sodium-calcium exchanger (NCX), a critical protein that regulates calcium ions in the heart and thereby alters the force of contraction, but only at the base of the ventricles (where the heart has its widest cross section). This effect accounts for the greater risk of long QT-related arrhythmias in women. [ABSTRACT FROM AUTHOR]

Abstract: The cholinergic system is crucial for cognitive processes and the deficient acetylcholine (ACh) function has been implicated in Alzheimer''s disease (AD). Inhibitors of acetylcholinesterase (AChE), which act to enhance cholinergic function by prolonging the action of endogenously released ACh, have been used as the major therapy of AD. To understand the functional roles of cholinergic enhancement in prefrontal cortex (PFC), a key brain region for cognition, we examined the impact of AChE inhibitors in PFC neurons on synaptic responses mediated by the NMDA receptor (NMDAR), an important player in learning and memory. We found that AChE inhibitors produced a strong and persistent reduction of the amplitude of NMDA receptor-mediated excitatory postsynaptic current (NMDAR-EPSC). This effect was mainly mediated by nicotinic ACh receptors, and through a Ca2+-dependent mechanism. Inhibition of extracellular signal-regulated kinases (ERK) abolished the regulation of NMDAR function by AChE inhibitors, suggesting the involvement of ERK. In the transgenic mouse model of AD overexpressing mutant β-amyloid precursor protein (APP), the effect of AChE inhibitors on NMDAR-EPSC was significantly impaired, which was associated with their diminished effect on ERK activation. Taken together, these results suggest that one of the key targets of endogenous ACh involved in cognition is the NMDAR-mediated transmission. Loss of the regulation of synaptic NMDAR responses by endogenous ACh may contribute to the cognitive deficiency in AD. [Copyright &y& Elsevier]

Chemodenitrification between Fe(II) and nitrite, an important nitrogen (N) cycling pathway, varies depending on the season, indicating the impact of ambient temperatures. However, the underlying mechanism for this occurrence has not been explained at a molecular scale. As an effective approach for studying N cycling, dual N O isotope fractionation was analyzed to reveal the reactions of temperature-dependent chemodenitrification. The kinetics of chemodenitrification under different temperatures showed that nitrite reduction rates and N 2 O production increased with temperature (5–35 °C). Lepidocrocite was identified as the secondary mineral of Fe(II) oxidation at 5, 15, and 25 °C, and goethite was observed at 35 °C. Further, the value of the O isotope enrichment factor (18 ε) decreased with increasing temperature while values of N isotope fractionation enrichment factor (15 ε) were less sensitive to temperature. The isotope fractionation ratios of O to N (18 ε :15 ε) were 1.00 ± 0.25, 0.75 ± 0.05, 0.54 ± 0.04, and 0.46 ± 0.06 at 5, 15, 25, and 35 °C, respectively, indicating that the temperature effect should be considered when dual N O isotope data are applied to distinguish chemodenitrification with biodenitrification. A kinetic model was established to correlate the rate constants of the elementary reactions during chemodenitrification with N O isotope fractionation. The intrinsic isotope fractionation of N O bond breakage during chemodenitrification was obtained. This study provides both qualitative and quantitative outcomes on temperature-dependent chemodenitrification. This study provides inputs for a better understanding of the role of chemodenitrification in effecting seasonal changes to the environment. [Display omitted] • The rate of nitrite reduction and N 2 O production increased with temperature. • The effect of temperatures on 18 ε and 15 ε was demonstrated. • The chemical and biological nitrite reduction can be distinguished with 18 ε : 15 ε. • Mass-transfer limitation was revealed using the elementary reaction kinetic model. [ABSTRACT FROM AUTHOR]

Abstract: A new ternary borate oxide, cesium barium borate, CsBaB3O6, has been synthesized by solid-state reaction at 700°C, and the single crystals were grown using CsF as a flux. The crystal structure has been determined by X-ray diffraction. It crystallizes in the trigonal space group P321 with a cell of dimensions a=12.469(3)Å, c=7.444(3)Å, α=90.00°, γ=120.00°, V=1002.3(5)Å3, Z=6. The fundamental building units of CsBaB3O6 are the B3O6 plane hexagonal rings, which are parallel to each other and stack along the c-axis, and the Cs and Ba atoms alternately occupy sites between the B3O6 sheets. A comparison of the structures of CsBaB3O6, β-BaB2O4 and CsBO2 is presented. [Copyright &y& Elsevier]

Abstract: A new nonlinear optical crystal calcium fluoroborate (Ca5(BO3)3F) has been grown successfully using LiF as a flux for the first time. Phase diagram of the pseudobinary Ca5(BO3)3F–LiF system within the composition range from 10 to 60wt% LiF was investigated by X-ray powder diffraction and differential thermal analysis. Our experiments demonstrated that the composition of LiF from 15 to 35wt% was beneficial to the growth of Ca5(BO3)3F crystals in Ca5(BO3)3F–LiF system. Transmission spectrum was recorded from 185 to 3000nm, which showed that the UV cutoff for Ca5(BO3)3F crystal was about 190nm. Second-harmonic generation efficiency was measured from Kurtz''s powder technique, which indicated that Ca5(BO3)3F could be phase matchable, and second-harmonic generation efficiency of Ca5(BO3)3F was about two times as large as that of KDP. Ca5(BO3)3F has potential application as a nonlinear optical material in UV region. [Copyright &y& Elsevier]

Interactions between dopamine and N-methyl-D-aspartate receptors (NMDARs) in prefrontal cortex (PEC) and other brain regions are believed to play an important role in normal mental function and neuropsychiatric disorders. In this study, we examined the regulation of NMDAR currents by the dopamine D1 receptor in PFC pyramidal neurons. Application of the D1 receptor agonist SKF81297 caused a prominent increase of the steady-state NMDA-evoked current in acutely isolated PFC pyramidal neurons. The D1 effect on NMDARs was independent of protein kinase A or protein phosphates 1, but was abolished by incubation of neurons in Ca2+-free medium. Intracellular application of the Ca2+ chelator, calmodulin, or calmodulin inhibitors largely prevented the D1 modulation of NMDAR currents. Moreover, inhibiting PKC activity or disrupting PKC association with its anchoring protein also significantly reduced the D1 effect on NMDAR currents. This upregulation of NMDAR activity by dopamine D1 receptors and the previous finding on up-regulation of dopamine D1 receptors by NMDAR acitvation provide a cellular mechanism for the receptors by NMDAR activation provide a cellular mechanism for the reciprocal interactions between D1 and NMDARs. These interactions may play an important role in modulating synaptic plasticity and thus in cognitive and emotional processes. [ABSTRACT FROM AUTHOR]

This study delves into the factors influencing the willingness of rural land transfers in different terrain areas, aiming to promote the improvement of land transfer institutions and accelerate the process of scale farming. Based on rural survey data from Anhui and Qinghai provinces in China, this research uses geographical detector and Binary Logistic Model to explore the differential factors affecting the willingness of farmers to participate in land contract transfer in the first and third terrain areas of China. The study examines four dimensions, including individual characteristics, family endowments, social support strategies, and geographical environment. The findings reveal the following: (1) By comparing the mean values, standard deviations, and coefficients of variation of the data from both provinces, it is evident that the indicators of individual characteristics, family endowments, social support strategies, and geographical environment differ significantly between the two provinces. This indicates substantial disparities in the basic attributes of farmers and their living environments. (2) The single-factor explanatory power significantly influencing farmers' willingness to engage in land transfer varies considerably and is statistically significant at the 1% level. The types of interaction between two factors mainly include dual-factor enhancement, nonlinear enhancement, single-factor nonlinear attenuation, and nonlinear attenuation. (3) There are commonalities and differences in the factors that significantly influence farmers' willingness to participate in land transfer in the two provinces. Common factors influencing farmers' land transfer willingness in both provinces include: the educational level of household heads, the health status of household heads, the number of family laborers, the arable land area, the differentiation of agricultural management objectives, the proportion of agricultural operating income, labor service economy, and relocation policies. Factors showing different influences include: the age of household heads, school-age children, the number of family members engaged in different occupations, the proportion of income from off-farm employment, minimum guarantee policies credit support, location distance, and terrain undulation. Therefore, in formulating land transfer policies, the government should prioritize significant driving factors influencing farmers' decision-making behavior in different regions. It is essential to develop and implement land transfer policies tailored to local conditions with the primary goal of safeguarding the rights and interests of the principal stakeholders, thus achieving sustainable land utilization. [ABSTRACT FROM AUTHOR]

Hexavalent chromium (Cr(VI)) could be sequestrated by soils via microbial reduction to Cr(III) and association with minerals, however, quantitative understanding of metal reducing bacteria on the coupled kinetics of Cr and Fe minerals is still lacking. Here, microbial-mediated ferrihydrite transformation and reductive sequestration of Cr(VI) were investigated with Shewanella oneidensis MR-1 under varying Cr/Fe ratios. Quantitative results depicted that the contents of magnetite from ferrihydrite transformation decreased from 70 % to 22 % after 288 h as Cr/Fe ratios increased from 0 to 8 × 10−3, and reductive transformation rates increased with decreasing Cr/Fe ratio. Elemental mapping and line scan analyses at nano-scale revealed that Cr(VI) was evenly combined within fresh ferrihydrite, and a part of produced Cr(III) was doped into the crystal lattice of magnetite and goethite. Cr may be sequestrated by secondary Fe minerals via structural substitution, surface complexation, and physical encapsulation. Microscopy-based results exhibited that more Fe minerals adsorbed on the surface of cell and less cells were lysed at low Cr/Fe ratios. Confocal laser scanning microscopy depicted that less cells were alive at high Cr/Fe ratios. The amplification of extracellular electron transfer-associated genes was downregulated as Cr/Fe ratios increased. The Cr/Fe ratios could affect cell activity, the combination with Fe minerals, and Mtr gene expression, thus controlling the reductive sequestration of Cr(VI) and phase transformation of ferrihydrite. A kinetic model has been established by combining elementary reductions, and it could well describe Cr(VI) reduction and Cr(III) incorporation under various Cr/Fe ratios during dissimilatory Fe reduction process. These findings could broaden our knowledge of quantifying the migration and transport of Cr in anoxic Cr-contaminated soil environments, and could be useful for simulating Cr dynamic behaviors in the natural soil, aquatic, and sediment environments. [ABSTRACT FROM AUTHOR]

Analyses of high-resolution seismic reflection, drilling, and well-log data were combined to identify and investigate deepwater fans developed in the eastern part of the Qiongdongnan Basin, South China Sea, during the Middle Miocene and their relationship to slope morphology. We identified three types of deepwater fans that developed on the northern continental margin of the South China Sea during the Middle Miocene: (1) those consisting of small canyons and depositional lobes; (2) those consisting of large canyons and depositional lobes; and (3) those consisting of distributary channels without depositional lobes. Sourced from deltaic sediments deposited on the northern continental shelf margin, the lithologies of the sediments in all fans are dominated by siltstone. The scale of development and the internal features are mainly controlled by the slope topography. The deepwater fans consisting of small canyons and depositional lobes developed on slopes with low gradient, caused by the continuous progradation of the shelf-edge towards the basin centre due to sediment transport in high-speed flows. The canyon heads developed in this setting are located below the shelf-break; these canyons are narrower, shallower, and shorter than those of the deepwater fans consisting of large canyons. Thus, the scale of the depositional lobes deposited by gravity flow through such canyons is smaller than that of deepwater fans with large depositional lobes. Deepwater fans consisting of large canyons and depositional lobes developed on steep narrow slopes, caused by rising shelf-edge trajectories due to the equilibrium between the sediment supply and subsidence rates. The canyon heads developed in this setting are located upon the shelf-break and extend toward the toe of the slope, incising the shelf-break; these canyons are wider, deeper, and longer than those of the deepwater fans consisting of small canyons. The scale of the depositional lobes deposited by gravity flows transported through such canyons is correspondingly larger than that of deepwater fans with small depositional lobes. Deepwater fans consisting of distributary channels without depositional lobes developed on gentler and wider slopes than slopes where small canyons and depositional lobes formed, owing to the low sediment supply. The deepwater distributary channels have a long transportation distance and wider distribution area, enabling the formation of large-scale deepwater fans. Depositional models for all three types of deepwater fans were postulated. • Three types of Middle Miocene deepwater fans in the Qiongdongnan Basin were identified. • The slope topography determines the internal features of these deepwater fans. • Sea-level fluctuations have a significant impact on the development of these deepwater fans. [ABSTRACT FROM AUTHOR]

In order to study the forming mechanism of metal jet under electromagnetic loading, numerical simulation for electromagnetic coupled jet forming was realized by using AUTODYN software with secondary development. Through secondary development, the magnetic pressure on the liner during the collapse process is calculated iteratively, which enables numerical simulation for electromagnetically coupled jets. The influence and threshold condition of electromagnetic parameters for jet forming are obtained through this. The results show that the head velocity and length of the jet are improved for liner without a tip. The electromagnetic parameters and structural parameters need to match with each other. The head velocity and effective length of the jet increase with the increase in wall thickness and cone angle. The liner diameter has little effect on the head velocity and effective length of the jet. The head velocity and effective length of the jet first increase and then decrease with the increase in cone radius. [ABSTRACT FROM AUTHOR]

While microbially mediated coupling process of nitrate reduction and Fe(II) oxidation (NRFO) plays important role in widespread nitrogen and iron biogeochemical cycles in the natural environments, the underlying mechanism of NRFO is still not clearly understood. Here, N and O isotope fractionation during microbial nitrate reduction by Pseudogulbenkiania sp. strain 2002 with or without Fe(II) were investigated. The nitrate reduction rate decreased substantially in the presence of Fe(II), and cells became encrusted with Fe(III) minerals. However, the N isotope enrichment factors (ε) with or without Fe(II) were identical within uncertainty (24.1 ± 2.4‰ and 25.1 ± 2.4‰), implying that Fe(II) oxidation had little influence on the extent of N isotope fractionation and that cell encrustation was unlikely to cause additional mass transfer limitation. Isotopic composition ratios of 18O to 15N (18 ε : 15 ε) were 0.73 ± 0.13 with and 0.50 ± 0.08 without Fe(II), close to reported values for nitrate reduction by periplasmic nitrate reductases, implying that enzymatic nitrate reduction mainly occurs in strain 2002's periplasmic space. A kinetic model based on elementary reactions was established, and rate constants of enzymatic nitrate reducing reactions were obtained in a living cell system. Combining dual N-O isotope fractionation analysis with kinetic modeling is a promising approach for interpreting diverse enzymatic pathways during NRFO processes. Unlabelled Image [ABSTRACT FROM AUTHOR]